tbuckley/cabot-search huggingface dataset:
Long-term follow-up results of the effects of chronotherapy and conventional chemotherapy combined with intensity modulated radiotherapy on dendritic cells and lymphocyte subsets in nasopharyngeal carcinoma.
Authors: Yang Minghui
Journal: Journal of Clinical Oncology (2022)

e18066 Background: In this study, we compared the effects of chronotherapy with conventional chemotherapy plus intensity modulated radiotherapy (IMRT)on dendritic cells and lymphocyte subsets in locoregionally advanced NPC. Methods: Analysis of 136 patients with treatment locoregionally advanced nasopharyngeal carcinoma enrolled, 68 patients were randomly assigned to the chronotherapy group and 68 patients to the conventional chemotherapy group, and all patients received 2-3 cycles of TPF induction chemotherapy plus 2-3 cycles of cisplatin concurrent chemoradiotherapy with the following schedules: docetaxel (DOC): 60mg / m2, ivgtt, D1 (03:30-04:30); Cisplatin (DDP): 60mg / m2, civ, d1-d5 (10:00-22:00); 5-fluorouracil (5-FU): 600mg / m2 / D 1, civ, d1-d5 (22:00-10:00); Synchronized DDP 100mg / m2, civ, D1 (10:00-22:00). Conventional group: Doc 60 mg / m2, ivgtt, D1; DDP 60mg/m2, ivgtt, d1; 5-FU 600mg/m2 /d 1, civ, d1-d5(120h); Synchronized DDP 100mg / m2, IVGTT, D1. Both groups were treated with IMRT at the same dose。 Lymphocyte and lymphocyte subsets were measured by flow cytometry before induction chemotherapy and 1 year versus 3 years after the end of concurrent chemoradiotherapy in patients, and changes in immune parameters, survival, and long-term toxicities were compared between the two groups. Results: One year after induction chemotherapy and concurrent chemoradiotherapy, the chronotherapy group showed higher plasma dendritic cells (PDC) than the conventional group (P &lt; 0.05). At 1 year after induction chemotherapy and concurrent chemoradiotherapy, CD4 +, activated CD4 +, activated CD8 +, CD3-CD16 +, PDC, and MDC were significantly higher (P &lt; 0.05) in both pre - and post-treatment groups, and at 1 year after induction chemotherapy and concurrent chemoradiotherapy in the conventional group (P &lt; 0.05). At 3 years after induction chemotherapy and concurrent chemoradiotherapy, CD4 +, activated CD4 +, activated CD8 +, CD4 + CD25 +, cd3-cd19 +, and CD3-CD16 + were significantly increased in the chronic group (P &lt; 0.05), and CD4 +, activated CD4 +, activated CD8 +, and CD4 + CD25 + were significantly increased in the conventional group (P &lt; 0.05). In the comparison of toxic effects between the two groups, the incidences of xerostomia and dysphagia in the group at 3 years after treatment were significantly lower than those in the conventional group (P &lt; 0.05). There were no significant differences in PFS, OS, DMFS, LRRFS between the two groups at 3 years (P &gt; 0.05). Conclusions: Chronotherapy with intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma more than conventional chemoradiotherapy reduces damage to dendritic cells and lymphocytes and alleviates toxic effects such as xerostomia and dysphagia at the same survival rate.
Comparison of AYA versus non-AYA ovarian cancer genomic landscape in NCI-MATCH trial.
Authors: Hari Sankaran, Yuri Kotliarov, Yingdong Zhao, Sarah M Temkin, Paul M. Williams, Chris Alan Karlovich, Brent Coffey, Biswajit Das, Ting-Chia Chang, Nita Seibel, James V. Tricoli, Ana F. Best, Robert James Gray, Victoria Wang, Zihan Wei, Stanley R. Hamilton, David R. Patton, Alice P. Chen, Lisa McShane
Journal: Journal of Clinical Oncology (2022)

e17617 Background: NCI-MATCH, a signal-finding precision medicine trial, centrally screened tumors from ̃6000 patients age &gt; 18 with refractory/relapsed cancer using Oncomine Comprehensive Assay (OCA) targeted gene panel. Screened cohort included a subset of patients with ovarian cancer age 18-39 yrs, overlapping adolescent and young adult (AYA) range (NCI consensus definition: 15-39 yrs). Objective of this study was to compare tumor genomic features of AYA to non-AYA ovarian cancers. Methods: Patient clinicopathologic, demographic, and tumor mutation (SNVs, Indels, CNVs by central OCA) data from NCI-MATCH were available. Analyses were restricted to mutation profiles generated by OCA version 2 (OCA v2), which assessed 143 genes and was used for most samples. Proportions of cases with mutations in each gene were compared for AYA and non-AYA groups by 2-sided Fisher’s exact tests. For each gene, association between age (continuous independent variable) and presence of mutation (binary dependent variable) was assessed using logistic regression. Benjamini-Hochberg adjusted p-values were computed; false discovery rate (FDR) was controlled at 10%. Results: Data from 455 ovarian cancers (437 epithelial, 18 stromal), including 21 AYA and 434 non-AYA cases, were included in this analysis. Among the 28 genes most frequently (in &gt; 6 patient tumors) mutated and altered, CTNNB1 was mutated in 9.5% of AYA patients compared to 0.9% in non-AYA (unadj. p=0.027) but failed to meet 10% FDR criterion (FDR-adj. p=0.7). KRAS mutation was more frequent in AYA than non-AYA but not significantly after adjustment (FDR-adj. p=0.7). Logistic regression results showed TP53 mutation was significantly associated with older age (FDR-adj. p&lt;0.0001), and ATM mutation was borderline associated with younger age (FDR-adj. p=0.052). No other differences, including in clinically actionable mutations ( BRCA1/2, MSH2), were observed. Table displays selected results. Conclusions: This preliminary study shows that no genes were mutated in significantly different proportion between AYA and non-AYA groups, but modeling age as a continuous variable highlighted known association of TP53 mutation with older age and a trend towards association of ATM mutation with younger age. More comprehensive tumor mutation profiling and analyses of additional tumor types may reveal further insights into rare AYA cancers. [Table: see text]
Time on treatment is prolonged in patients utilizing an ePRO based digital symptom monitoring platform in the community setting.
Authors: Christina Parrinello, Geoffrey Calkins, Lavi Kwiatkowsky, Eric S. Schaefer, J. Thaddeus Beck, Amy R. Ellis, Sibel Blau, Bijoy Pankaj Telivala, Michael A. Kolodziej
Journal: Journal of Clinical Oncology (2022)

1528 Background: Earlier and more effective management of cancer-related symptoms and treatment-related toxicities might improve the survival of patients receiving systemic anti-cancer therapy. One potential mechanism for improved outcomes could be prolonging time on therapy. We have previously reported on the successful real-world implementation of an electronic patient-reported outcomes (ePRO) tool in a community oncology practice. We now report on the impact of the tool on time on therapy for common anti-cancer treatments. Methods: We evaluated time on treatment across three community oncology practices that have implemented Expain, an EMR-integrated ePRO system which enables remote symptom monitoring during therapy. We compared drug-specific cohorts of patients that had been enrolled on the ePRO tool with a concurrent cohort of patients not enrolled on the ePRO platform. We examined time on treatment using a Kaplan Meier (KM) approach. Analysis was confined to patients with no prior administration of the parenteral therapeutic agent or a 90-day treatment-free washout period; and to patients with at least three months of potential follow-up. Analysis was only conducted for drugs with at least 80 patients in the Expain arm. Results: In each drug-specific cohort, the distribution of age, sex, and primary cancer diagnosis was similar in patients enrolled vs not enrolled on the ePRO (Mann-Whitney and Chi-square p &gt; 0.05 except for the rituximab cohort which had more males in the ePRO cohort [67 vs 52%]). The impact of the ePRO-based symptom monitoring system on time on therapy was statistically significant for 5 agents. Conclusions: We confirm in the community setting the observation that digital symptom monitoring can increase time on therapy. We believe this is due to more effective management of treatment related toxicities, as well as more effective management of malignancy related or comorbid medical emergencies which might interrupt or lead to the discontinuation of therapy. We are evaluating the robustness of these results after using various methods to address any potential non-comparability of the cohorts. We are also examining the impact of prolonging time on treatment on survival. [Table: see text]
CPGJ602 plus mFOLFOX6 as first-line treatment for patients with KRAS/NRAS/BRAF wild-type metastatic colorectal cancer: A randomized phase II study.
Authors: Jianming Xu, Bangwei Cao, Kangsheng Gu, Yuxian Bai, Wei Li, Jingdong Zhang, Caigang Liu, Zuoxing Niu, Liangming Zhang, Haijun Zhong, SuXia Luo, Jian-Wei Zhou, Tianshu Liu, Yanhong Gu, Jingguan Lin, Yanhong Deng, Chuangqi Chen, Yunfeng Li, Xiuli Yang, Bihui Li
Journal: Journal of Clinical Oncology (2022)

3574 Background: CPGJ602 is a recombinant anti-EGFR human-mouse chimeric monoclonal antibody. CPGJ602 plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) may have efficacy in KRAS/NRAS/BRAF wild-type metastatic colorectal cancer. Methods: In this open-label, randomized trial, patients who had received no previous treatment were randomly assigned (2:2:1) to receive CPGJ60（325mg/m 2 , q2w) plus mFOLFOX6 (biweekly group), CPGJ602 (400 mg/m 2 initial dose followed by 250 mg/m 2 /week thereafter) plus mFOLFOX6 (weekly group) or cetuximab (400 mg/m 2 initial dose followed by 250 mg/m 2 /week thereafter) plus mFOLFOX6 (cetuximab group). All subjects received treatment up to 16 weeks. The primary endpoint was the best overall response (BOR) at 16 weeks. The second endpoints were DCR, DOR, PFS, safety. Results: As of Dec 30, 2021, 76 patients were enrolled (30 in biweekly group, 32 in weekly group and 14 in control group). The best overall response achieved at 16 weeks was 76.7% (23/30, 95% CI 60.3% - 92.0%),78.1% (25/32, 95% CI 62.5% - 92.5%) and 78.6% (11/14, 95% CI 49.2% - 95.3%) in the biweekly group, weekly group and cetuximab group, respectively. The confirmed overall response rate at 16 weeks was 60%(18/30), 71.9%(23/32) and 57.1%(8/14) in the biweekly group, weekly group and cetuximab group, respectively. The PFS rates at 16 weeks were 81.5% (95% CI 57.7% -92.6%), 96.8% (95% CI 79.2%-99.5%), 81.3% (95% CI 41.5%- 95.2%) in the biweekly group, weekly group and cetuximab group, respectively. The most common adverse events were a decreased neutrophil count (60%，78.1% and 71.4% in the biweekly group, weekly group and cetuximab group respectively), decreased white-cell count (53.3%, 78.1% and 71.4% respectively), decreased platelet count (40.0%, 40.6% and 42.9% respectively), and elevated serum aspartate aminotransferase (43.3%, 37.5% and 35.7% respectively). Conclusions: CPGJ602 plus mFOLFOX6 could be an option for KRAS/NRAS/BRAF wild-type metastatic colorectal cancer. Clinical trial information: NCT04466254.
Impact of provider education on hepatitis B screening practices prior to patients receiving cancer treatment.
Authors: Michael Adashek, Jacob Culver, Carolyn Anne Carrera
Journal: Journal of Clinical Oncology (2022)

1539 Background: Hepatitis B virus (HBV) reactivation is a known side effect of CD20 targeted therapies with complications ranging from transient hepatitis to fulminant hepatic failure and death. In 2020 the American Society of Clinical Oncology (ASCO) expanded its provisional clinical opinion (PCO) to recommend HBV screening for all patients prior to receiving non-hormonal systemic anti-cancer therapies and if positive, offer viral prophylaxis or treatment. We assessed in a single-institution prospective study if a provider-led educational session on the 2020 ASCO PCO was effective in increasing HBV screening among patients receiving systemic non-hormonal anti-cancer therapies. Methods: An educational session for 30 minutes on the benefits outlined in the ASCO 2020 PCO discussing hepatitis B screening was held at a community-based hematology/oncology practice in Michigan. HBV screening panel was added to pre-chemotherapy lab order sets. Provider compliance with HBV screening recommendations was assessed monthly. Patients with positive HBV serology were identified and referred to Hepatology for monitoring and anti-viral treatment/prophylaxis as indicated. Data from 1,984 patient encounters for cancer treatment utilizing either chemotherapy or rituximab among 12 providers from March of 2020 to December 2021. Multivariate and logistic regression analysis was performed. Results: The educational intervention on the best practices of screening for Hepatitis B was effective in raising screening. Prior to intervention, 79.3% of all patients receiving rituximab (N = 140) and 15.7% of all patients receiving chemotherapy (N = 1277) had documentation for Hepatitis B before cancer treatment. Post-intervention hepatitis B testing increased both among patients receiving rituximab to 95.8% (N = 48) and chemotherapy to 29.9% (N = 519). In summary, prior to intervention, just 22.0% of 1,417 patient encounters had documentation for Hepatitis B screening before undergoing a treatment regimen. Post-intervention this level was raised to 35.45% (= 37.41,). In this study, 3 cases (0.5%) of acute and 12 cases (2.0%) of chronic HBV were identified from the 603 tested patients. A mixed effects logistic regression model controlling for treatment type and provider found patient encounters occurring post-intervention were 2.30 times more likely to be screened (OR = 2.30, 95% CI = [1.81, 2.93], p &lt; 0.001). Conclusions: Our single educational session discussing the 2020 ASCO PCO and testing techniques for HBV was effective at increasing the odds of screening 2.3 times among patients receiving non-hormonal systemic anticancer therapies adjusting for therapy and provider. This may serve as a model for other implementations of PCOs. Further research will assess long-term oncologic outcomes of those identified with HBV and effects of anti-viral interventions.
Diagnostic accuracy of the CxPREVENTIVE Colon model for early detection of colorectal cancer.
Authors: Sergio J Calleja, Édgar C Patiño
Journal: Journal of Clinical Oncology (2022)

e15518 Background: Despite different available methods for colorectal cancer (CRC) screening and their proven benefits, morbidity, and mortality of this malignancy are still high, partly due to technical limitations and low compliance with screening. The aim of the present study was to assess the diagnostic accuracy for early detection of CRC using a modeling algorithm based on multiple blood and urine biomarkers. Methods: In this retrospective cohort study, clinical and blood and urine markers-based algorithms with predefined cutoff values were applied to a generally healthy asymptomatic outpatient cohort of adults aged 50 years or older undergoing colonoscopy and histopathology for routine colorectal cancer screening. We used a modeling algorithm based on two different frameworks (Multiple Biomarkers Disease Activity Algorithm MBDAA [Bioprognos], and Artificial Intelligence Recursive Algorithm AIRA [Mintlot] both in Barcelona, Spain). Both algorithms compute information from a wide number of analytes, tumor markers (AFP, CA 19.9, CA 72.4, CA 125, CEA, Cyr61, NGAL, EGFR and 8-OHdG), and additional clinical data (age, weight, height, and BMI). MBDAA includes Barcelona Criteria (four criteria to correctly interpret the cause of the increase in tumor markers, benign or malignant, defined by the Spanish Society of Clinical Biochemistry and Molecular Pathology, Commission of Biological Markers of Cancer). To assess the association between the modelling algorithm and downstream diagnosis we used logistic regression to compute receiver operating characteristic curves (ROC). Exact binomial confidence limits were calculated to test accuracy, sensitivity, and specificity. Results: 221 people (median age 63 yr. [IQR 49-77]; 107 [49%] women and 114 [51%] men) who underwent colonoscopy at the Juan Ramón Jiménez Hospital (Huelva, Spain), were included in this analysis. Based on colonoscopy and histopathologic findings, CRC was diagnosed in 45 (20%) patients, colonic polyposis in 56 (25%), inflammatory bowel disease in 37 (17%), and absence of pathological findings (control group) was seen in 83 (38%). The diagnostic intervention for CRC yielded an area under the curve (AUC) of 1 among the entire specimen set, accuracy 1 (95% CI 0.996,1), Se 1 (0.988, 1) and Sp 1 (0.997, 1). Besides, the algorithm also performed very well in the identification of polyps with an accuracy 1 (95% CI, 0.967 to 1), Se of 1 (0.991, 1) and of Sp 1 (0.996, 1), as well in the diagnosis of inflammatory bowel disease with an accuracy of 1 (0.968 to 1), Se of 1 (0.986, 1) and Sp of 1 (0.997, 1). Conclusions: Using colonoscopy as a gold standard, our data suggest that an innovative newly designed non-invasive blood and urine-based biomarker algorithm CxPREVENTIVE Colon may provide a timely diagnosis of CRC with very high accuracy. Our findings warrant further investigation, and we are planning large-scale (n 10,000), fully powered study to inform clinical practice.
A first-in-human, phase 1b study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of neoadjuvant use of ph-762 administered intratumorally in subjects with advanced melanoma.
Authors: Caroline Robert, Severine Roy, Benjamin Cuiffo, James Cardia, Simon Paul Fricker
Journal: Journal of Clinical Oncology (2022)

TPS9608 Background: Antibodies targeting immune checkpoints such as PD-1 and CTLA-4 has shown significant benefit in late-stage melanoma. But further improvements in therapeutic options are still required. Two approaches for improving the outcome of immunotherapy with checkpoint inhibitors are neoadjuvant treatment and local intratumoral (IT) injection. IT immunotherapy uses the tumor as its own vaccine to activate the immune system, priming an anti-tumor immune response and generating systemic tumor responses, whilst minimizing systemic exposure and off-target toxicities. Neoadjuvant therapy provides the opportunity for preoperative disease shrinkage with the potential to improve surgical morbidity. There is currently no neoadjuvant standard of care for resectable, advanced melanoma patients. PH-762 is a potent RNAi molecule targeting PD-1 with structural and chemical modifications conferring properties suitable for IT administration, including an optimized cell and tissue uptake profile. Pharmacology studies show potent in vitro silencing of PD-1 associated with T cell activation, and robust, dose-dependent in vivo inhibition of tumor growth in syngeneic tumor models. Methods: The purpose of this study is to evaluate the safety of neoadjuvant use of PH-762 administered by IT injection in subjects with resectable stage IIIB/IIIC/IIID or IV melanoma, to determine the recommended Phase 2 dose, PK after IT injection, and potential immunologic and pathologic tumor responses. Study treatment constitutes of once weekly injections with PH-762 into one designated tumor lesion for 4 weeks prior to surgical excision at 5-6 weeks after the initial injection, with up to 5 dose levels tested in a serial fashion in cohorts of 3 or more subjects. Eligible subjects will have at least one resectable melanoma deposit that is large enough to allow IT injection, and that can undergo repeated biopsy. Subjects with active brain metastases, leptomeningeal disease, uveal melanoma, and auto-immune disease are excluded. The dose of PH-762 will be normalized to tumor volume to ensure an equivalent local dose (tumor tissue concentration). Post tumor excision, subjects will be followed-up for 6 weeks. Primary endpoint is to determine a safe dose of PH-762 assessed by incidence of Dose Limiting Toxicities (DLT) prior to tumor resection. Bayesian optimal interval (BOIN) design will be employed to evaluate escalating doses of PH-762 to determine the Maximum Tolerated Dose based on occurrence of DLT. Tumor changes will be evaluated per RECIST criteria (version 1.1 and iRECIST version adapted for use with IT therapy) and pathological response. Immunological response in tumor tissue and blood samples will be assessed as secondary endpoints. Enrollment commenced in February 2022. Clinical trial information: 2021-002859-10.
<i>PBRM1</i> genomic alterations as a predictive biomarker to immune checkpoint inhibitors (ICI) and/or anti-angiogenic therapies (anti-VEGF) in metastatic renal cell carcinoma (mRCC): A systematic review and meta-analysis.
Authors: Lucio Ghiglione, Laia Fernandez-Mañas, Laura Ferrer-Mileo, Caterina Aversa, Marta Garcia de Herreros, Juan Carlos Laguna, Teresa Gorria, Mercedes Marin, Natalia Jiménez, Aleix Prat, Joan Maurel, Begona Mellado, Oscar Reig
Journal: Journal of Clinical Oncology (2022)

e16515 Background: Combination therapy with ICI and anti-VEGF has become the standard first-line (1L) therapy for metastatic clear cell RCC (mccRCC). However, about 25% of patients (pts) are long responders to anti-VEGF monotherapy. PBRM1 genomic alterations (ga) are present in around 40% mccRCC pts and contradictory results have been reported about its role as a predictive biomarker. We performed a systemic review and meta-analysis to assess the role of PBRM1 ga as a predictive biomarker of response to ICI, anti-VEGF, or its combination. Methods: A systematic review of PubMed, EMBASE, Cochrane, and Web of Science databases was performed (February 2022) to identify studies involving mRCC pts who received systemic therapy and had PBRM1 status and clinical outcomes reported. Study design, baseline characteristics, treatment data, and hazard ratios (HRs) with 95% confidence intervals (CI) for each clinical outcome were extracted. HRs were combined across studies using a random effect model. The primary endpoint was to correlate PBRM1 status with progression-free survival (PFS) to anti-VEGF, ICI, or its combination. Results: The systematic review included 12 out of 892 publications (n = 6528 pts), 98% (n = 6372) mccRCC; 3297 pts (51%) treated with anti-VEGF monotherapy, 1574 (24%) ICI (PD-L1 (n = 1019, 65%) or CTLA4 + anti PD-L1 (n = 555, 35%)), 997 pts (15%) anti-VEGF + ICI, and 660 pts (10%) with other therapies (e.g., mTORi or INF). PBRM1 status was assessed by NGS in 3841 pts (59%) and detected in 1595 (41%). Nine out of 12 publications were considered for the meta-analysis; excluding those with duplicated pts or lack of information. Six studies (n = 2593 pts) evaluated PBRM1 status in first-line (1L) therapies, including anti-VEGF in monotherapy (n = 1487, 57%) and ICI (n = 1106, 43%; combined w/anti-VEGF (n = 773), w/CTL4 (n = 262) or in monotherapy (n = 71)). In 1L setting, PBRM1 ga pts had longer PFS under monotherapy with anti-VEGF ( PBRM1 ga 44%; HR = 0.74 (95% CI, 0.62 - 0.88), p &lt; 0.01) but not under ICI ( PBRM1 ga = 42%; HR = 1 (95% CI, 0.85 - 1.17), p = 0.38) nor ICI + anti-VEGF treatment ( PBRM1 ga = 33.5%; HR = 0.93 (95% CI, 0.73 - 1.18), p = 0.56). Two studies evaluated PBRM1 status in second line (2L) ICI-treated mRCC pts (n = 517 pts). PBRM1 ga pts had longer PFS under ICI in 2L ( PBRM1 ga = 36%, HR = 0.64 (95% CI, 0.49 - 0.83), p = 0.0007). Conclusions: mRCC pts with PBRM1 ga showed longer PFS to 1L anti-VEGF and 2L ICI therapy, supporting its role as a predictive biomarker. Anti-VEGF + ICI combination de-escalation strategies merits further investigation in PBRM1 ga mRCC patients.